Department of Obstetrics and Gynecology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Department of Gynecology, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Tokyo, Japan.
Virol J. 2020 Mar 6;17(1):32. doi: 10.1186/s12985-020-01306-0.
Human papillomavirus (HPV) infection is a primary cause of cervical cancer. Although epidemiologic study revealed that carcinogenic risk differs according to HPV genotypes, the expression patterns of HPV-derived transcripts and their dependence on HPV genotypes have not yet been fully elucidated.
In this study, 382 patients with abnormal cervical cytology were enrolled to assess the associations between HPV-derived transcripts and cervical intraepithelial neoplasia (CIN) grades and/or HPV genotypes. Specifically, four HPV-derived transcripts, namely, oncogenes E6 and E6*, E1^E4, and viral capsid protein L1 in four major HPV genotypes-HPV 16, 18, 52, and 58-were investigated.
The detection rate of E6/E6* increased with CIN progression, whereas there was no significant change in the detection rate of E1^E4 or L1 among CIN grades. In addition, we found that L1 gene expression was HPV type-dependent. Almost all HPV 52-positive specimens, approximately 50% of HPV 58-positive specimens, around 33% of HPV 16-positive specimens, and only one HPV18-positive specimen expressed L1.
We demonstrated that HPV-derived transcripts are HPV genotype-dependent. Especially, expression patterns of L1 gene expression might reflect HPV genotype-dependent patterns of carcinogenesis.
人乳头瘤病毒（HPV）感染是宫颈癌的主要病因。尽管流行病学研究表明致癌风险因 HPV 基因型而异，但 HPV 衍生转录本的表达模式及其对 HPV 基因型的依赖性尚未完全阐明。
本研究纳入了 382 例宫颈细胞学异常患者，以评估 HPV 衍生转录本与宫颈上皮内瘤变（CIN）分级和/或 HPV 基因型之间的关系。具体而言，我们研究了四种主要 HPV 基因型（HPV 16、18、52 和 58）中的四种 HPV 衍生转录本，即致癌基因 E6 和 E6*、E1^E4 和病毒衣壳蛋白 L1。
E6/E6*的检出率随 CIN 进展而增加，而 E1^E4 或 L1 的检出率在 CIN 分级中无明显变化。此外，我们发现 L1 基因表达与 HPV 型别相关。几乎所有 HPV 52 阳性标本、约 50%的 HPV 58 阳性标本、约 33%的 HPV 16 阳性标本以及仅一个 HPV18 阳性标本表达 L1。
我们证明了 HPV 衍生转录本与 HPV 基因型相关。特别是，L1 基因表达模式可能反映了 HPV 基因型依赖性的致癌模式。
